We propose to establish a CFS Cooperative Research Center. The central theme and goal of the Center is to develop a standardized path to the evaluation of the CFS patient in order to categorize the patient in diagnostic subsets. This central theme is the foundation upon which the Proposed Projects, Core, and Developmental Fund stand, and around which each revolves. This proposal represents a response to RFA 91-AI-02 by a multidisciplinary team of investigators representing a number of departments at the New Jersey Medical School and the Department of Microbiology at the Uniformed Services University of the Health Sciences and collaborators from the Medical College of Pennsylvania, Yale and the NIH. The purpose of our proposed Center is to integrate the diagnostic capabilities of a group of virologists and an immunologist with state-of-the-art methodological tools with a group of physician-scientists expert at physiological evaluation. This approach starts at the level of the gene for evaluating cytokine function, moves to the virological level to assay for a number of candidate viruses, then to the cellular level, to develop in vitro models for viral reactivation and cytokine production, then up to the organ level to assess pulmonary, metabolic, and autonomic nervous system function, and finally culminates with the whole patient. Our plan is to use our viral and immunological diagnostic abilities to divide CFS patients into normal and abnormal groups [over the 4 year duration of the Center we expect to further subdivide the latter group based on updated results). Then we would submit the patients with appropriate controls to a testing battery addressing the following symptoms of CFS: cognitive dysfunction, depression, abnormal body temperature, fatigue, and lightheadedness or dizziness. We hypothesize that patients in the abnormal group will have one or more of the following: signs of organicity on neuropsychological testing, abnormal circadian temperature rhythms, abnormal muscle metabolism particularly when tested on the day after exercise, and abnormal metabolic, pulmonary and autonomic function during physical and psychological stress. These highly collaborative studies represent integration across the wide domain of medicine, psychology and physiology. In addition to the Projects, funds have been set aside to permit funding a mini-grant for Pilot Studies. One Core Unit has been developed to provide central administrative and data analytic services to the Research Projects.